Investigation of the Association of Multimodal Neuroimaging and Peripheral Biomarkers With Executive Functions and Emotional Regulation in Adolescents With Attention-Deficit/Hyperactivity Disorder

Attention-deficit/hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by difficulties in attention, hyperactivity, and impulsivity. Although alterations in neural networks and peripheral biological processes have been investigated separately, the relationships among functional brain connectivity, peripheral biomarkers, executive functions, and emotional regulation in adolescents with ADHD remain incompletely understood.

The primary aim of this study is to investigate the relationships among resting-state functional brain connectivity, peripheral serum biomarkers, executive functions, and emotional regulation in adolescents with ADHD and to compare these findings with those of healthy controls. The study will focus particularly on resting-state functional connectivity within and between brain networks, including the default mode network (DMN), executive control network (ECN), and salience network (SN).

The study will include adolescents aged 10 to 18 years with ADHD and age- and sex-matched healthy controls. Participants will undergo standardized clinical and psychological assessments, resting-state functional magnetic resonance imaging (fMRI), and peripheral blood sampling. Serum concentrations of brain-derived neurotrophic factor (BDNF), cortisol, interleukin-1 alpha (IL-1α), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and interferon-gamma (IFN-γ) will be measured using enzyme-linked immunosorbent assay (ELISA).

Executive functioning, emotional regulation, behavioral characteristics, and clinical symptoms will be assessed using standardized clinical and behavioral assessment instruments. Resting-state fMRI data will be processed using standard preprocessing procedures, including motion correction, coregistration, normalization, smoothing, denoising, and band-pass filtering. Functional connectivity analyses will be conducted using independent component analysis and/or seed-based correlation approaches.

The study will examine whether alterations in resting-state functional connectivity and peripheral biomarker levels differ between adolescents with ADHD and healthy controls and whether these biological measures are associated with executive functioning, emotional regulation, and clinical characteristics. Associations among functional connectivity measures, serum biomarkers, and behavioral and clinical scores will also be investigated.

The study is designed to contribute to a more comprehensive understanding of the neurobiological mechanisms underlying ADHD in adolescence by integrating neuroimaging, peripheral biological, and behavioral measures.

Inclusion criteria

• Age 10-18 years, including ages 10 and 18.
• Diagnosis of attention-deficit/hyperactivity disorder (ADHD) according to DSM-5 criteria.
• Clinically normal intellectual capacity (IQ >80).
• Predominantly right-handed.
• No acute or chronic inflammatory disease.

Healthy Control Group:

• Age 10-18 years, including ages 10 and 18.
• No psychiatric diagnosis according to DSM-5 criteria.
• Clinically normal intellectual capacity (IQ >80).
• Predominantly right-handed.
• No acute or chronic inflammatory disease.

Exclusion criteria

• Age younger than 10 or older than 18 years.
• Intellectual disability (IQ <80).
• Hydrocephalus or herniation.
• Predominantly left-handed.
• History of possible traumatic brain injury.
• Current or past neurological or serious medical disease (e.g., epilepsy).
• Autism spectrum disorder.
• Psychotic disorder.
• Mood disorder.
• Conduct disorder.
• Active anxiety disorder or substance use disorder.
• Presence of an acute or chronic inflammatory disease.